title: Enhanced cartilage regeneration in MIA/CD-RAP deficient mice.
abstract: Melanoma inhibitory activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from chondrocytes. It was identified as the prototype of a family of extracellular proteins adopting an SH3 domain-like fold. In order to study the consequences of MIA/CD-RAP deficiency in detail we used mice with a targeted gene disruption of MIA/CD-RAP (MIA-/-) and analyzed cartilage organisation and differentiation in in vivo and in vitro models. Cartilage formation and regeneration was determined in models for osteoarthritis and fracture healing in vivo, in addition to in vitro studies using mesenchymal stem cells of MIA-/- mice. Interestingly, our data suggest enhanced chondrocytic regeneration in the MIA-/- mice, modulated by enhanced proliferation and delayed differentiation. Expression analysis of cartilage tissue derived from MIA-/- mice revealed strong downregulation of nuclear RNA-binding protein 54-kDa (p54(nrb)), a recently described modulator of Sox9 activity. In this study, we present p54(nrb) as a mediator of MIA/CD-RAP to promote chondrogenesis. Taken together, our data indicate that MIA/CD-RAP is required for differentiation in cartilage potentially by regulating signaling processes during differentiation.
authors.affiliation: Institute of Pathology, University of Regensburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schmid
authors.forename: S
authors.initials: S
authors.lastname: Schiffner
authors.forename: A
authors.initials: A
authors.lastname: Opolka
authors.forename: S
authors.initials: S
authors.lastname: Grässel
authors.forename: T
authors.initials: T
authors.lastname: Schubert
authors.forename: M
authors.initials: M
authors.lastname: Moser
authors.forename: A-K
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D000818:Animals; D002356:Cartilage / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020219:Chondrogenesis; D004195:Disease Models, Animal; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012038:Regeneration; D055758:SOX9 Transcription Factor / Q000378:metabolism; D004268:DNA-Binding Proteins
chemical_list: D016326:Extracellular Matrix Proteins; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins; D055758:SOX9 Transcription Factor; C513263:Mia protein, mouse; C527933:Sox9 protein, mouse; C500331:Nono protein, mouse; D004268:DNA-Binding Proteins